Supplementary Material for: Growth Kinetics in Von Hippel-Lindau-Associated Renal Cell Carcinoma

<i>Objective:</i> To evaluate the growth kinetics of renal cell carcinoma (RCC) in von Hippel-Lindau (VHL) disease in a large trial by CT/MRI scan. VHL disease is a multisystemic disorder predisposing to renal cysts and cancer. There is a general assumption that VHL-associated RCC presents slower growth rates than sporadic RCC. <i>Patients and Methods:</i> We describe growth kinetics of 96 renal tumours in 64 VHL patients with analysed germline mutation (54/64 treated, 10/64 active surveillance) over a mean follow-up of 54.9 months. We calculated tumour volume, growth rate, multiplication of tumour volume per year and overall, as well as tumour volume doubling time. <i>Results:</i> The mean growth rate of 96 tumours was 4.4 mm/year (SD 3.2, median 4.1 mm/year), mean volume doubling time was 25.7 months (SD 20.2, median 22.2 months). We saw a median 1.4-fold increase in tumour volume per year. At treatment time point, VHL kidneys comprised 39% tumour and 15.7% cyst volume fraction. We saw no correlation between tumour size and growth parameters. <i>Conclusion:</i> VHL-associated RCC show large variances in tumour growth behaviour. Compared to the literature, in our study the growth rates (mm/year) of RCC in VHL disease did not differ from those of sporadic RCC. Fast tumour growth increases the risk for metastases.

<i>研究目标：</i> 本研究旨在通过CT/MRI扫描，在大型临床试验中评估希佩尔-林道（von Hippel-Lindau, VHL）病相关肾细胞癌（renal cell carcinoma, RCC）的生长动力学。VHL病是一种多系统疾病，患者易罹患肾囊肿与肾癌。学界普遍认为，VHL相关肾细胞癌的生长速度慢于散发性肾细胞癌。
<i>患者与方法：</i> 本研究纳入64例携带明确胚系突变的VHL病患者，共计96个肾脏肿瘤，平均随访时长为54.9个月；其中54例患者接受治疗，10例患者接受主动监测。研究人员计算了肿瘤体积、生长速率、年肿瘤体积倍增倍数等总体参数，同时计算了肿瘤体积倍增时间。
<i>研究结果：</i> 96个肿瘤的平均生长速率为4.4 mm/年（标准差3.2，中位值4.1 mm/年），平均体积倍增时间为25.7个月（标准差20.2，中位值22.2个月）。研究观察到肿瘤体积年增长中位倍数为1.4倍。在接受治疗时，VHL病患者的肾脏中肿瘤体积占比为39%，囊肿体积占比为15.7%。未发现肿瘤大小与生长参数之间存在相关性。
<i>研究结论：</i> VHL相关肾细胞癌的肿瘤生长行为存在较大异质性。与现有文献报道相比，本研究中VHL病相关肾细胞癌的生长速率（mm/年）与散发性肾细胞癌并无显著差异。肿瘤快速生长会增加转移风险。